Optically active 1-[3,5-bis(trifluoromethyl)phenyl]ethyl group is important as an element unit of compounds useful as medicaments, agricultural chemicals, and the like, and 1-bromo-1-[3,5-bis(trifluoromethyl)phenyl]ethane is an extremely useful compound as a raw material for preparing compounds containing that group. For example, there has been disclosed use of 1-bromo-1-[3,5-bis(trifluoromethyl)-phenyl]ethane as a raw material for the preparation of compounds that act as an NK-1 receptor antagonist (Non-patent documents 1 and 2). However, although the compound has the aforementioned important usefulness, only a method for preparing racemate of 1-bromo-1-[3,5-bis(trifluoromethyl)phenyl]ethane has been known, and no publication is found that specifically reports a method for preparing optically active compound thereof.
Racemate of 1-bromo-1-[3,5-bis(trifluoromethyl)phenyl]ethane can be synthesized by the method shown in Scheme 1 mentioned below (Patent document 1). This method comprises the steps of converting 3,5-bis(trifluoromethyl)acetophenone into an alcohol compound by reduction with sodium borohydride in methanol, and brominating the resulting alcohol compound by using phosphorus tribromide in toluene.

Racemate of 1-bromo-1-[3,5-bis(trifluoromethyl)phenyl]ethane can also be synthesized by the method shown in Scheme 2 mentioned below (Non-patent document 3). This method comprises the step of converting 3′,5′-bis-(trifluoromethyl)acetophenone into an alcohol compound by reduction with sodium borohydride in methanol, and brominating this alcohol compound by a treatment with hydrobromic acid and sulfuric acid. However, Patent document 1 and Non-patent document 3 do not specifically disclose any method for preparing optically active 1-bromo-1-[3,5-bis(trifluoromethyl)phenyl]ethane.

One of enantiomers of optically active 1-[3,5-bis(trifluoromethyl)phenyl]-ethanol with high optical purity can be obtained by subjecting bis-3′,5′-(trifluoromethyl)phenylacetophenone to an asymmetric reduction reaction, or subjecting bis-3,5-(trifluoromethyl)benzaldehyde to an asymmetric methylation reaction. Therefore, if the alcohol of high optical purity as a starting material can be converted into 1-bromo-1-[3,5-bis(trifluoromethyl)phenyl]ethane with maintaining the high optical purity of the starting material, such a preparation method can be an industrially convenient and efficient preparation method. However, any method for efficiently preparing 1-bromo-1-[3,5-bis(trifluoromethyl)phenyl]ethane by using such an optically active alcohol as a starting material with maintaining high optical purity of the alcohol is not known so far.
As a general method for brominating hydroxyl group, there is known a method of converting hydroxyl group of an alkyl alcohol or benzyl alcohol into a leaving group such as sulfonic acid ester group, and brominating the result by a substitution reaction with bromide ion (Non-patent document 4). It has also been reported that if phosphorus tribromide is made to react with optically active 1-phenylethanol at low temperature in the presence of an excessive amount of pyridine in diethyl ether, 1-phenylbromoethane can be obtained in a high yield (conversion ratio, 93.9%; Non-patent document 5).

Further, there have also been reported a method of exchanging hydroxyl group for a halogen by using 1,2-dibromo-1,1,2,2-tetrachloroethane and triphenylphosphine (Non-patent document 6), and a method of exchanging hydroxyl group for a halogen by using N-bromosuccinimide and dimethyl sulfide (Non-patent document 7). However, it is not known so far that 1-bromo-1-[3,5-bis(trifluoromethyl)phenyl]ethane can be prepared by applying these methods to optically active 1-[3,5-bis(trifluoromethyl)phenyl]ethanol with maintaining high optical purity of the starting material.

In addition, as a method for preparing an optically active compound, there is generally performed optical resolution of racemate by chiral column chromatography. However, since 1-bromo-1-[3,5-bis(trifluoromethyl)phenyl]ethane is highly reactive, a method utilizing optical resolution of racemate to provide an optical isomer may possibly be accompanied by decomposition and racemization of the objective substance, and it is expected that an optical isomer cannot be stably supplied. Also in Non-patent document 2 mentioned above, racemate of 1-bromo-1-[3,5-bis(trifluoromethyl)-phenyl]ethane is used as a raw material without any treatment, and there is employed a method of performing optical resolution of the resulting mixture of diastereomers in two steps to obtain the optically active objective substance.
